The overall goal of research in this laboratory is to model neurodegenerative diseases in stem cell based models.
Specifically the neurodegeneration and regeneration in neurites are investigated. The two diseases studied are Parkinson’s disease (PD) and hereditary spastic paraplegia (HSP), a specific genetic form of motor neuron disease.
Hereditary spastic paraplegia (HSP)
This Junior Research Group is specifically interested in understanding the involvement of selected hereditary spastic paraplegia (HSP) proteins in axonal degeneration. HSP is a genetic condition leading to corticospinal tract degeneration. HSPs selectively involve a length-dependent axonopathy from long projecting corticospinal motorneurons (CSMN), while sparing the neuronal cell bodies. CSMN is studied to understand the molecular mechanisms crucial for axonal maintenance and degeneration. The models used are human induced pluripotent stem cell (hiPSC)-derived neurons generated from HSP patient’s fibroblasts.
The overall aim is to understand the normal function of selected HSP proteins, to determine how abnormality of these functions lead to the disease and to use this knowledge to rationally design new therapeutic strategies for the disorder.
Parkinson’s disease (PD)
Protein aggregation of misfolded proteins is associated with several neuropathological conditions in humans, including PD, Alzheimer’s disease, and Huntington’s disease. Lewy Bodies, an aggregated fibrillar form of multiple proteins (among them alpha-synuclein) are the major pathological hallmark in PD. It has been suggested that a small oligomeric species of the protein, rather than its aggregated fibrillar counterpart, is the toxic culprit in PD. The impact of oligomerisation in models of synucleinopathies is investigated. The data indicate a correlation between the extent of oligomer formation in vitro and toxicity in vivo. Specifically, the interest is in studying the mechanism and functional consequences of oligomerization for neurite degeneration. Better understanding of cell-neurite-oligomer interactions in brain cells will allow testing of specific compounds for better treating PD.